Platelets and Inflammation: Relations between Platelet Counts and Markers of Inflammation (original) (raw)

Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection

Cardiovascular & Haematological Disorders - Drug Targets(formerly Current Drug Targets - Cardiovascular & Hematological Disorders), 2008

Platelets play a complex role in hemostasis and thrombosis. The expression of multiple membrane receptors, both constitutive and activation-dependent, mediates platelet adhesion and aggregation at sites of vascular lesion. Platelet activation leads to exocytosis of granular constituents, release of newly synthesized mediators, and discharge of membrane-bound transcellular signaling molecules. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelet participation in other physiological or pathological processes including inflammation, malignancy and the immune response. Platelet receptors such as GPIb/IX/V, P-selectin, P-selectin glycoprotein ligand 1, CD40 and the IIbß3 integrin, crucial to hemostasis, have been implicated in the progression of such inflammatory conditions as atherosclerosis, rheumatoid arthritis and inflammatory bowel disease, in the progression and metastatic spread of malignancies, and in the immune response to bacterial challenge. The release of platelet granular contents, including adhesive proteins, growth factors and chemokines/cytokines, that serve to facilitate hemostasis and wound repair, also function in acute and chronic inflammatory disease and in tumor cell activation and growth. Platelets contribute to host defence as they recognise bacteria, recruit traditional immune cells to the site of infection and secrete bactericidal mediators. The primary focus of this review is the "non-haemostatic" functions of platelets in physiological and pathological states.

Current viewpoints on platelet contribution to inflammation

Inflammation is an underlying feature of a variety of human diseases. Because inflammatory diseases are a major cause of morbidity and mortality in developed countries, understanding the interaction of the most important factors involved is an important challenge. Although platelets are widely recognized as having a critical role in primary hemostasis and thrombosis, basic and clinical evidence increasingly identifies these enucleated cells as relevant modulators, as both effector and target cells, of the inflammatory response. The cross-talk between platelets, endothelial cells and leukocytes in the inflammatory milieu mat be seen as a double-edged sword which functions not only as an effective first-line defense mechanism but may also lead to organ failure and death in the absence of counter-regulation systems. The molecular mechanisms involved in the reciprocal activation of platelets, endothelial cells and leukocytes are beginning to be elucidated. In the light of the existing d...

The prowess of platelets in immunity and inflammation

Thrombosis and Haemostasis

SummaryPlatelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease....

Role of Platelets in Inflammation and Cancer: Novel Therapeutic Strategies

Basic & Clinical Pharmacology & Toxicology, 2014

Platelets play a central role in inflammation through their direct interaction with other cell types, such as leucocytes and endothelial cells, and by the release of many factors, that is, lipids [such as thromboxane (TX)A 2 ] and proteins (a wide number of angiogenic and growth factors) stored in a-granules, and adenosine diphosphate (ADP), stored in dense granules. These platelet actions trigger autocrine and paracrine activation processes that lead to leucocyte recruitment into different tissues and phenotypic changes in stromal cells which contribute to the development of different disease states, such as atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The signals induced by platelets may cause pro-inflammatory and malignant phenotypes in other cells through the persistent induction of aberrant expression of cyclooxygenase (COX)-2 and increased generation of prostanoids, mainly prostaglandin (PG)E 2 . In addition to cardiovascular disease, enhanced platelet activation has been detected in inflammatory disease and intestinal tumourigenesis. Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer. All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigenesis) and endothelial (in tumourigenesis and atherothrombosis) injury. Extensive translational medicine research is necessary to obtain a definitive mechanistic demonstration of the platelet-mediated hypothesis of colon tumourigenesis. The results of these studies will be fundamental to support the clinical decision to recommend the use of lowdose aspirin, and possibly other antiplatelet agents, in primary prevention, that is, even for individuals at low cardiovascular risk.

Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

Advances in Hematology, 2012

Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

Role of platelets in inflammation

Dicle Medical Journal / Dicle Tip Dergisi, 2012

İnflamasyon patolojik etkenlere karşı canlı dokular tarafından oluşturulan, patojeni uzaklaştırmaya yarayan ve iyileşme sürecini başlatan son derece önemli bir olaydır. Mikroorganizmalar, fiziksel ve kimyasal travmalar, termal yaralanma, iskemi ve immün reaksiyonlar inflamasyon nedeni olarak gösterilebilir. Plateletler, nükleusa sahip olmayan ve kemik iliğinde megakaryositlerden üretilen hücreler olup kanamanın durdurulması ve hemostazın devamında rol almasının yanısıra inflamasyonda da önemli rol almaktadır. Nötrofil ve makrofajlara benzer şekilde, inflamasyon mekanizmasına etki edecek çeşitli sitokin üretimi ve salınımı yaparlar. Bu derlemede inflamasyonda plateletlerin rolleri ve inflamasyonun plateletler üzerine etkileri tartışılacaktır.

Human platelets—danger sensing and inflammation: Helpful or harmful?

Platelets are non-nucleated cellular elements that play a role in haemostasis, innate immunity, and inflammation. Platelet-linked inflammation seems essentially related to the capacity of platelets to secrete cytokines, chemokines, and related molecules upon stimulation or state change. Moreover, platelets display receptors for numerous types immune effectors and regulators. This secretory function confers to platelets a regulatory role in immunity. Platelets also exhibit non-self infectious danger detection molecules on their surfaces, particularly from the Toll-like receptor (TLR) family; through TLR expression, platelets can bind infectious agents and also deliver different signals for the secretion of cytokines and chemokines. Platelets may therefore be regarded as a neglected component of immune cell regulators, and they contribute to some interesting aspects in bridging innate and adaptive immunity. Further, platelets may sense several types of infectious pathogens and limit m...

Immune functions of platelets

Thrombosis and haemostasis, 2014

This review collects evidence about immune and inflammatory functions of platelets from a clinician's point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Platelets promote chronic inflammatory reactions (e.g. in atherosclerosis), modulate acute inflammatory disorders such as sepsis and other infections (participating in the host defense against pathogens), and contribute to exacerbations of autoimmune conditions (like asthma or arthritis). It would hence be obsolete to restrict a description of platelet functions to thrombosis and haemostasis--platelets clearly are the most abundant cells with immune functions in the circulation.

Platelets and Immune Responses During Thromboinflammation

Frontiers in Immunology, 2019

Besides mediating hemostatic functions, platelets are increasingly recognized as important players of inflammation. Data from experiments in mice and men revealed various intersection points between thrombosis, hemostasis, and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation but also contributing to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest. Future insights into platelet biology are to be expected. This research will potentially offer novel opportunities for therapeutic intervention in diseases featuring platelet abundance.